title: Possible involvement of pirfenidone metabolites in the antifibrotic action of a therapy for idiopathic pulmonary fibrosis.
abstract: Pirfenidone (PFD) is the first and only clinically used antifibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). This study evaluated the antifibrotic effects of two metabolites of PFD, 5-hydroxypirfenidone (PFD-OH) and 5-carboxypirfenidone (PFD-COOH), on WI-38 cells in an in vitro lung fibroblast model. The inhibitory effects of PFD-OH and PFD-COOH on transforming growth factor-β1 (TGF-β1)-induced collagen synthesis in WI-38 cells were evaluated by measuring intracellular hydroxyproline, a major component of the protein collagen. PFD-OH and PFD-COOH at 300 and 1000 µM concentrations significantly decreased the TGF-β1-induced hydroxyproline content in WI-38 cells. These results indicate that PFD-OH and PFD-COOH have antifibrotic activities, which inhibit collagen synthesis in fibroblasts. This study suggests that the concentrations of PFD and its metabolites should be considered in clinical therapy for IPF.
authors.affiliation: Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy.
authors.forename: Kohei
authors.initials: K
authors.lastname: Togami
authors.forename: Yukimune
authors.initials: Y
authors.lastname: Kanehira
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tada
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011728:Pyridones / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; D053773:Transforming Growth Factor beta1; D003094:Collagen; C093844:pirfenidone; D006909:Hydroxyproline